Lithium Mechanism of Action (MOA)

1.       1^st Line Tx Bipolar Disorder

Works like Na+. Blocks Na Channels

-Cell can’t become too positive

-Cell can’t become too negative

Mood Stabilizer (not acute Dz)

Blocks Relapse & acute Maniac Events

2.       Blocks ADH receptors V2

→ Nephro DI

SIADH Tx

3.       Fools kidney: Holds Li, let go Na

→Hyponatremia

Affects Electrolytes & ion transport

4.       Fools Thyroid (Resembles I)

→Hyponatremia

5.       Fools PTH receptors:

a.       ↑Ca+2, ↓PO4

6.       Phospho Inositol Cascade Inhibition

Inhibits dephospholiration of IP3->IP2, IP2-IP1 and IP1-IP

(inositol recycling steps → ↓PIP2)

7.       ↓DA & NE turnover (↓DA ↓ NE ↑Serotonin)

(IP3 is recycled back to PIP2 by the enzymes inositol monophosphate phosphatase (IMPase) and inositol polyphosphatase phosphatase (IPPase); both of which are inhibited by lithium)

Adrenergic Drugs

Ionization and Clearence

Inulin changes examples

Signal transduction proteins

These are the different type of receptors and related G-protein-linked 2nd messengers that they use.

Cholinomimetics

Some Cholinergic agonists and their functions

Neostigmine → Myasthenia Gravis, PO & neurogenic ileus and urinary retention, Reversal of NM junction blockage

Pyridostigmine → Myasthenia Gravis (long acting)

Edrophonium → Myasthenia Gravis Diagnosis (extremely short acting)

Physostigmine → Glaucoma (crosses BBB), and atropine overdose

Echothiopate → Glaucoma

Galantamine/ Donepezil / Rivastigmine/ Tacrine → Alzheimer's

Organophosphates

Steroid Synthesis

Neurotransmitter changes

Anxiety:	↑NE,  ↓GABA,  ↓Serotonin (5-HT)
Depression:	↓NE,  ↓Serotonin (5-HT), ↓Dopamine
Alzheimer's dementia:	↓ Ach
Huntington's disease:	↓GABA, ↓Ach
Schizophrenia:	↑Dopamine.
Parkinson's disease:	↓Dopamine,  ↑Ach, ↑Serotonin (5-HT)

Cyanide Poisoning

Cytocrome P450

	INDUCERS	INHIBITORS
Effect on drugs	Decreased (fail to respond)	Increased (risk of toxicity)
Anticonvulsivants	Barbiturates (Phenobarbital) Phenytoin Carbamazepine Ethosuximide	Valproic Acid
Antibiotics	Rifampin	Chloramphenicol Quinolones (Ciprofloxacin) Macrolides (Erythromycin) Sulfonamides (TMT SMX) Isoniazid (INH)
Antifungals	Griseofulvin	Ketoconazole Fluconazole
Alcohol	Chronic alcoholism	Acute alcoholism
Fruits/ Plants	St. John's Wort	Grapefruit
Antiarrythmics	Quinidine
Sterols	Glucocorticois
Antiulcerous		Cimetidine Omeprazole
Antivirals		Ritonavir (HIV protease inhs)
Antitumoral		Cyclosporin

Pharmacology

Some renal Findings

Multiple myeloma Ischemic tubular necrosis Acute pyelonephritis Hypersensitivity interstitial nephritis Papillary necrosis & Chronic interstitial nephritis Aminoglycoside toxicity Lead nephropathy Urate nephropathy Acute Tubular Necrosis (renal azotemia)

Eosinophilic casts (Bence-Jones prot), in tubular lumens Ischemic tubular necrosis WBC Casts Drug-induced interstitial nephritis NSAID-associated nephropathy Aminoglycoside toxicity Chronic tubulointerstitial nephritis Needle shaped monosodium urate crystals are seen in the interstitium and tubular lumens Heavy metal poisoning with lead or mercury (produces Fanconi Sd)

Aspirin Intoxication

Aspirin poisoning will produce respiratory alkalosis initially then will produce metabolic acidosis.

Others producing Metabolic acidosis are:

Increased anion Gap (MUD PILES) M- Methanol U- Uremia D- DKA P- Paraldehyde or phenformin I- Iron tablets or INH L- Lactic Acidosis E- Ethylene glycol S- Salicilates

Normal anion Gap Diarrhea Renal Tubular Acidosis (alkaline urine ph < 5.5) Hyperchloreima

Insulin Release in Pancreatic β Cell

DO NOT GIVE THIAZIDES TO HYPERGLYCEMIC, HYPERLIPIDEMIC, & HYPERURICEMIC PATIENS
Remember that normally insulin will inhibit HSL (Hormone Sensitive Lipase) required for the breakdown of stored TG in adipose tissue. Since thiazides stop the production of ATP on the pancreatic β cell, preventing the realease of insulin required for keeping TG inside of adipose tissue, this drugs are not given to hyperlipidemic patients.

Renal Physiology

Antiarrhythmics

Some mnemonics:

Class IB Lido Me Toca
Class IC FEP
Class III SIBAD

•Class I:
IA: Police Department Questioned
IB: The Little Man
IC: For Pushing Ecstasy

•Class I
IA: Double Quarter Pounder
IB: Lettuce, Tomato, Mayo, Pickles
IC: Fries Please

•Also remember:
Beta 1 selective blockers: AMEBA
atenolol
metoprolol
esmolol
betaxolol
acebutalol

IA: Police Department Questioned IB: The Little Man IC: For Pushing Ecstasy

IA: Double Quarter Pounder IB: Lettuce, Tomato, Mayo, Pickles IC: Fries Please

BLOOD VESSEL INNERVATION

NICOTINIC RECEPTORS

BLADDER & LUNGS INNERVATION

KIDNEY AND PANCREAS INNERVATION (Mnemonic)

The way Vivi recalls the kidney and pancreas innervation is assigning the number 1 to the organ kidney (because is the #1 arterial pressure regulator organ) and #2 to the pancreas (because type II Diabetes is the most common diabetes ja ja)

Both organs have α and ß receptors

In general α receptors in these two organs decrease and ß receptors increase secretion/release of its hormones.

There you go!

Kidney:
α1 receptors ↓ Renin Release
ß1 receptors ↑ Renin Release

Pancreas:
α2 receptors ↓ Insulin Secretion
ß2 receptors ↑ Insulin Secretion